The Clinical Studies of the NIMH Collaborative Program on the Psychobiology of Depression involves an interrelated and coordinated group of investigations conducted on two samples drawn from five centers -- mood disordered probands and their relatives. This application seeks to continue the follow-up of the samples and to implement several new, but related aims: 1) investigation of the long-term course of illness in probands, relatives, spouses and controls; 2) determination of predictors of onset and recurrence in the same samples; 3) investigation of suicidal behavior, mortality and medical morbidity; 4) investigation of personality disorders in the samples, including validity, joint familial transmission with mood disorders, and influence on clinical course of mood disorders; 5) a genetic linkage study of unipolar and bipolar families; 6) investigation of stability of diagnosis on familial modes of transmission; 7) further investigation of secular trends in the occurrence of mood disorders. These aims have important public health, clinical and research implications.